chr6-117301021-G-A

Position:

• chr6-117301021-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378902.1(ROS1):​c.6668C>T​(p.Ser2223Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ROS1 NM_001378902.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

Genes affected

ROS1 (HGNC:10261): (ROS proto-oncogene 1, receptor tyrosine kinase) This proto-oncogene, highly-expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057365984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROS1	NM_001378902.1	c.6668C>T	p.Ser2223Phe	missense_variant	43/44	ENST00000368507.8	NP_001365831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROS1	ENST00000368507.8	c.6668C>T	p.Ser2223Phe	missense_variant	43/44	5	NM_001378902.1	ENSP00000357493	P1
ROS1	ENST00000368508.7	c.6686C>T	p.Ser2229Phe	missense_variant	42/43	1		ENSP00000357494

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.8
DANN	Benign	0.80
DEOGEN2	Benign	0.094	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.15
Sift	Benign	0.38	T;T
Sift4G	Benign	0.25	T;T
Polyphen		0.0	B;.
Vest4		0.14
MutPred		0.36		Loss of disorder (P = 0.0179);.;
MVP		0.17
MPC		0.026
ClinPred		0.11	T
GERP RS		2.2
Varity_R		0.087
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-117622184;